Analysis of hepatitis B virus quasispecies changes during emergence and reversion of lamivudine resistance in liver transplantation

This report describes nucleotide sequence analysis of part of the polymeras e gene of hepatitis B virus (HBV) during the development of lamivudine-resi stant HBV in five patients who received lamivudine treatment in conjunction with liver transplantation. Samples from patients were analysed before, du ring and after drug treatment in conjunction with serum HBV quantification by PCR. Lamivudine resistance was found to be associated with L526M and M55 0V changes in two patients and M5501 change in three patients. Other change s associated with lamivudine resistance in some patients were V5091, A546V, S565A and A568T. The effects on HBV surface antigen are also described. So me patients were subsequently treated with famciclovir and/or ganciclovir w ith variable outcomes. In two out of three patients who stopped lamivudine treatment, reversion (partial or complete) to wild-type virus was observed after about 5 months. In contrast, a complex mixture of mutant viruses emer ged in a third patient who stopped lamivudine treatment.